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Newly discovered gene may predict aggressive ovarian cancer

Johns Hopkins Kimmel Cancer Center researchers have linked alterations in a gene, called Rsf-1, to the most deadly ovarian cancers. The scientists say the discovery is the first to establish a role for the gene in ovarian cancer and may lead to a test that can predict, early on, which patients will develop aggressive disease.

"We hope new therapies can be tailored to target Rsf-1, in the same way that Herceptin for breast cancer attacks the Her2/neu gene pathway," says Tian-Li Wang, Ph.D., assistant professor of gynecology/obstetrics and oncology at Johns Hopkins.

The scientists' findings, reported in the September 27 issue of the Proceedings of the National Academy of Sciences, described a surge in the number of Rsf-1 gene copies in 13.2 percent (16 of 121) of high grade ovarian cancers, but not in low grade or benign ovarian tumors. Normally, cells contain two copies of every gene. In cancer cells, the copying mechanism goes haywire creating dozens of gene copies in a process called amplification.

Survival data showed that the 16 patients with Rsf-1 amplification fared worse than patients without the ramped-up genes, living an average of 29 months versus 36 months.

Hopkins scientists discovered their first clues to Rsf-1 after sifting through the entire genome of seven ovarian cancer cell lines using a method developed three years ago with their Johns Hopkins colleague, Victor Velculescu, M.D., Ph.D. The search tool digitizes genetic code and pinpoints abnormalities within precise regions of the DNA, much the way global mapping tools zoom in on specific addresses.

According to Ie-Ming Shih, M.D., Ph.D., associate professor of pathology and oncology, who co-directs the laboratory with Wang, other gene typing methods can identify abnormalities within wide areas of the genome, but the tool used for this study, called digital karyotyping, is far more precise. "It's like narrowing down our search from the entire State o
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Contact: Vanessa Wasta
wastava@jhmi.edu
410-955-1287
Johns Hopkins Medical Institutions
29-Sep-2005


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